The VPS35 D620N mutation impairs retromer complex assembly at endosomal membranes, disrupting the retrieval of GCase-containing vesicles from endosomes back to the lysosome. Under physiological conditions, the retromer recognizes a specific sorting motif on GCase (possibly within its cytosolic tail) and directs it toward the lysosome via the CLIP1-positive tubular network. The VPS35 D620N mutation specifically destabilizes the retromer-cargo interaction without affecting overall complex integrit
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.78
Evidence
0.75
Novelty
0.72
Feasibility
0.75
Impact
0.75
Druggability
0.00
Safety
0.00
Competition
0.00
Data
0.00
Reproducible
0.50
KG Connect
0.19
Score Breakdown
Dimension
VPS35 Retromer Dysfunction Cre
Mechanistic
0.780
Evidence
0.750
Novelty
0.720
Feasibility
0.750
Impact
0.750
Druggability
0.000
Safety
0.000
Competition
0.000
Data
0.000
Reproducible
0.500
KG Connect
0.187
Evidence
VPS35 Retromer Dysfunction Creates a GCase Trafficking Bottl